| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
HDAC
Histone deacetylase (HDAC). GSK3117391 is an HDAC inhibitor that modulates the activity of histone deacetylase enzymes. HDACs are enzymes that remove acetyl groups from histone proteins, thereby regulating gene expression. Inhibition of HDACs leads to increased histone acetylation and altered gene transcription, which can have anti-inflammatory and anti-proliferative effects. |
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| ln Vitro |
GSK3117391 is a potent HDAC inhibitor. Specific IC50 values for HDAC inhibition are not detailed in the available literature. As an HDAC inhibitor, it would be expected to increase histone acetylation and modulate gene expression in target cells. The compound has been investigated for its potential in treating rheumatoid arthritis.
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| ln Vivo |
GSK3117391 has been investigated in preclinical and clinical studies for the treatment of rheumatoid arthritis. It has reached Phase 1 clinical trials, indicating that it has shown sufficient promise in preclinical models to warrant evaluation in humans. Specific in vivo efficacy data are not detailed in the available literature.
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| Enzyme Assay |
In vitro HDAC inhibition assays for GSK3117391 involve measuring the activity of HDAC enzymes in the presence of varying concentrations of the compound. The enzyme is incubated with a fluorogenic or radiolabeled substrate, and the deacetylation reaction is quantified. The IC50 value is determined from the dose-response curve. These assays are typically performed using recombinant HDAC enzymes or nuclear extracts.
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| Cell Assay |
In vitro cell-based assays for GSK3117391 assess its effects on histone acetylation in cultured cells. Cells are treated with GSK3117391, and the levels of acetylated histones are measured by Western blotting or ELISA. The compound's effects on cell proliferation, inflammation, and gene expression can also be evaluated. The compound is soluble in DMSO.
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| Animal Protocol |
In vivo studies of GSK3117391 have been conducted in animal models of rheumatoid arthritis, supporting its progression to Phase 1 clinical trials. The compound is typically administered orally. Endpoints would include measurement of inflammatory markers, joint inflammation, and disease severity. Specific protocols are not detailed in the available literature.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for GSK3117391 are not extensively reported in the available literature. As a small molecule HDAC inhibitor with a molecular weight of 403.52, it is expected to have reasonable oral bioavailability. Detailed PK parameters such as half-life, Cmax, and AUC are available from clinical studies but are not detailed in the available sources.
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| Toxicity/Toxicokinetics |
Specific toxicological data for GSK3117391 are not detailed in the available literature. As a clinical candidate that has reached Phase 1 trials, its safety profile has been evaluated in preclinical toxicology studies. Common toxicities associated with HDAC inhibitors include gastrointestinal effects, fatigue, and hematological abnormalities.
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| References | |
| Additional Infomation |
GSK-3117391 is being studied in the clinical trial NCT02965599 (Efficacy, safety, tolerability, pharmacokinetics and pharmacodynamics of GSK3117391 in patients with rheumatoid arthritis).
GSK3117391 is a clinical candidate that has been investigated for the treatment of rheumatoid arthritis. It is a histone deacetylase (HDAC) inhibitor extracted from patent WO/2008040934 A1. The compound is also known as ESM-HDAC391 and HDAC-IN-3. It is not an FDA-approved therapeutic agent. |
| Molecular Formula |
C22H33N3O4
|
|---|---|
| Molecular Weight |
403.523
|
| Exact Mass |
403.247
|
| Elemental Analysis |
C, 65.48; H, 8.24; N, 10.41; O, 15.86
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| CAS # |
1018673-42-1
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| Related CAS # |
1018673-42-1
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| PubChem CID |
53630042
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| Appearance |
Light yellow to khaki solid powder
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| Density |
1.2±0.1 g/cm3
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| Index of Refraction |
1.566
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| LogP |
2.55
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| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
10
|
| Heavy Atom Count |
29
|
| Complexity |
518
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
O(C([C@]([H])(C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H])N([H])C([H])([H])C1=C([H])N=C(C([H])([H])C([H])([H])C(N([H])O[H])=O)C([H])=C1[H])=O)C1([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H]
|
| InChi Key |
AFDPFLDWOXXHQM-NRFANRHFSA-N
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| InChi Code |
InChI=1S/C22H33N3O4/c26-20(25-28)13-12-18-11-10-16(14-23-18)15-24-21(17-6-2-1-3-7-17)22(27)29-19-8-4-5-9-19/h10-11,14,17,19,21,24,28H,1-9,12-13,15H2,(H,25,26)/t21-/m0/s1
|
| Chemical Name |
cyclopentyl (2S)-2-cyclohexyl-2-[[6-[3-(hydroxyamino)-3-oxopropyl]pyridin-3-yl]methylamino]acetate
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| Synonyms |
GSK3117391; GSK 3117391; GSK-3117391; GSK-3117391A; GSK3117391A; GSK 3117391A; HDAC-IN-3; HDAC-IN 3; HDAC-IN3
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| HS Tariff Code |
2934.99.03.00
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 50~81 mg/mL (123.9~200.7 mM)
Ethanol: ~15 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.20 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.20 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.20 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4782 mL | 12.3910 mL | 24.7819 mL | |
| 5 mM | 0.4956 mL | 2.4782 mL | 4.9564 mL | |
| 10 mM | 0.2478 mL | 1.2391 mL | 2.4782 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT02965599 | Terminated | Drug: GSK3117391 Drug: Placebo |
Arthritis, Rheumatoid | GlaxoSmithKline | December 27, 2016 | Phase 2 |
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